The modifier-of-deaf waddler (mdfw) is a hearing susceptibility locus which confers progressive hearing loss to CBy-dfw2J/+ heterozygous. Neither homozygosity at the mdfw locus nor heterozygosity at the dfw2J locus alone are sufficient to cause the observed hearing impairment indicating a synergistic interaction between the two loci. Recently, we identified the dfw gene and showed that mutations in the plasma membrane Ca2+ ATPase 2 gene (Atp2b2) are the cause of hearing loss and imbalance in two mutant strains of deaf waddler. We are now focusing on identifying the second component (mdfw) of this genetic interaction. By positional cloning we will seek to identify and characterize the function of the mdfw gene. During the last year we expanded the mapping cross, fine mapped the mdfw critical region and started the construction of a Bacterial Artificial Chromosome (BAC) based physical map.